Cartridge with laminated manifold

ABSTRACT

A circuit with electrical interconnect for external electronic connection and sensor(s) on a die are combined with a laminated manifold to deliver a liquid reagent over an active surface of the sensor(s). The laminated manifold includes fluidic channel(s), an interface between the die and the fluidic channel(s) being sealed. Also disclosed is a method, the method including assembling a laminated manifold including fluidic channel(s), attaching sensor(s) on a die to a circuit, the circuit including an electrical interconnect, and attaching a planarization layer to the circuit, the planarization layer including a cut out for the die. The method further includes placing sealing adhesive at sides of the die, attaching the laminated manifold to the circuit, and sealing an interface between the die and fluidic channel(s).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/626,022 filed on Feb. 3, 2018 and Dutch Patent Application No.N2020616 filed on Mar. 19, 2018. The entire contents of each of theaforementioned applications are incorporated herein by reference.

BACKGROUND

Current cartridges for biological or chemical analysis do not handleliquid reagents in an efficient manner. For example, the fluidic path islong, going from the reagent storage area through a conventionalmanifold to the die, the die including semiconductor sensor(s). Thearrangement may slow the analysis and results in large volumes of washreagent used for each cycle.

Therefore, there is a need for a more efficient fluidic path design.

SUMMARY

The shortcomings of pre-existing approaches may be overcome andadditional advantages are provided through the provision, in one aspect,of an apparatus. The apparatus comprises a circuit and at least onesensor on a die coupled to the circuit, the circuit comprising anelectrical interconnect for external electrical connection, and alaminated manifold attached to the circuit to deliver a liquid reagentover an active surface of the at least one sensor, the laminatedmanifold comprising at least one fluidic channel, an interface betweenthe die and the at least one fluidic channel being sealed.

In accordance with yet another aspect, a method is provided. The methodcomprises assembling a laminated manifold, the laminated manifoldcomprising at least one fluidic channel, attaching at least one sensoron a die to a circuit, the circuit comprising an electricalinterconnect, and attaching a planarization layer to the circuit, theplanarization layer comprising a cut out for the die. The method furthercomprises placing sealing adhesive at sides of the die, attaching thelaminated manifold to the circuit, and sealing an interface between thedie and the at least one fluidic channel, the laminated manifold andattached circuit together comprise an assembly.

BRIEF DESCRIPTION OF THE DRAWINGS

These, and other objects, features and advantages of this disclosurewill become apparent from the following detailed description of thevarious aspects thereof taken in conjunction with the accompanyingdrawings, in which:

FIG. 1 is a perspective view of one example of a cartridge with a sensorand laminated manifold, useable for, e.g., biological or chemicalanalysis, in accordance with one or more aspects of the presentdisclosure.

FIG. 2 is a blown-up view of one example of the laminated manifold ofFIG. 1, showing the various layers of the laminated manifold, inaccordance with one or more aspects of the present disclosure.

FIG. 3 is a perspective view of one example of the sensor in relation tothe laminated manifold and the circuit, in accordance with one or moreaspects of the present disclosure.

FIG. 4 is a perspective view of one example of a cross-section of thesensor area taken across a line of FIG. 3, in accordance with one ormore aspects of the present disclosure.

FIGS. 5-10 depict various stages of constructing the cartridge ofFIG. 1. FIG. 5 is a perspective view of one example of the circuit withthe sensor attached thereto, in accordance with one or more aspects ofthe present disclosure.

FIG. 6 depicts attaching a planarization layer to the circuit of FIG. 5via, for example, using a bonding layer including a pressure-sensitiveadhesive, in accordance with one or more aspects of the presentdisclosure.

FIG. 7 depicts dispensing and curing a bridge adhesive to the structureof FIG. 6, in accordance with one or more aspects of the presentdisclosure.

FIG. 8 depicts one example of attaching a laminated manifold (e.g., asdescribed with respect to FIG. 2) to the circuit of FIG. 7 via, forexample, a bonding layer (FIG. 2) including a pressure-sensitiveadhesive, in accordance with one or more aspects of the presentdisclosure.

FIG. 9 depicts one example of forming wire bonding to the structure ofFIG. 8, encapsulating the wire bonding and attaching a flow cellchannel, in accordance with one or more aspects of the presentdisclosure.

FIG. 10 depicts one example of connecting the structure of FIG. 9 to thereagent rotor and the cartridge body, in accordance with one or moreaspects of the present disclosure.

DETAILED DESCRIPTION

Aspects of the present disclosure and certain features, advantages, anddetails thereof, are explained more fully below with reference to thenon-limiting examples illustrated in the accompanying drawings.Descriptions of well-known materials, fabrication tools, processingtechniques, etc., are omitted so as not to unnecessarily obscure therelevant details. It should be understood, however, that the detaileddescription and the specific examples, while indicating aspects of thedisclosure, are given by way of illustration only, and are not by way oflimitation. Various substitutions, modifications, additions, and/orarrangements, within the spirit and/or scope of the underlying inventiveconcepts will be apparent to those skilled in the art from thisdisclosure.

Approximating language, as used herein throughout the specification andclaims, may be applied to modify any quantitative representation thatmay permissibly vary without resulting in a change in the basic functionto which it is related. Accordingly, a value modified by a term orterms, such as “about” or “substantially,” is not limited to the precisevalue specified. In some instances, the approximating language maycorrespond to the precision of an instrument for measuring the value.

The terminology used herein is for the purpose of describing particularexamples only and is not intended to be limiting. As used herein, thesingular forms “a”, “an” and “the” are intended to include the pluralforms as well, unless the context clearly indicates otherwise. It willbe further understood that the terms “comprise” (and any form ofcomprise, such as “comprises” and “comprising”), “have” (and any form ofhave, such as “has” and “having”), “include (and any form of include,such as “includes” and “including”), and “contain” (and any form ofcontain, such as “contains” and “containing”) are open-ended linkingverbs. As a result, a method or device that “comprises,” “has,”“includes” or “contains” one or more steps or elements possesses thoseone or more steps or elements, but is not limited to possessing onlythose one or more steps or elements. Likewise, a step of a method or anelement of a device that “comprises,” “has,” “includes” or “contains”one or more features possesses those one or more features, but is notlimited to possessing only those one or more features. Furthermore, adevice or structure that is configured in a certain way is configured inat least that way, but may also be configured in ways that are notlisted.

As used herein, the term “connected,” when used to refer to two physicalelements, means a direct connection between the two physical elements.The term “coupled,” however, can mean a direct connection or aconnection through one or more intermediary elements.

As used herein, the terms “may” and “may be” indicate a possibility ofan occurrence within a set of circumstances; a possession of a specifiedproperty, characteristic or function; and/or qualify another verb byexpressing one or more of an ability, capability, or possibilityassociated with the qualified verb. Accordingly, usage of “may” and “maybe” indicates that a modified term is apparently appropriate, capable,or suitable for an indicated capacity, function, or usage, while takinginto account that in some circumstances the modified term may sometimesnot be appropriate, capable or suitable. For example, in somecircumstances, an event or capacity can be expected, while in othercircumstances the event or capacity cannot occur—this distinction iscaptured by the terms “may” and “may be.”

As used herein, unless otherwise specified, the approximating terms“about,” “substantially” and the like, used with a value, such asmeasurement, size, etc., means a possible variation of plus or minus tenpercent of the value.

As used herein, the terms “bond,” “bonded” and “bonding” refer to twothings being joined securely together using an adhesive or bonding agenttogether with a heat process or pressure. As used herein, the term“attach” refers to joining two things together, with or without the useof a fastener (e.g., screw, adhesive or bonding agent, etc.) Thus, theterm “bond” is a subset of the term “attach.”

Reference is made below to the drawings, which are not drawn to scalefor ease of understanding, wherein the same reference numbers are usedthroughout different figures to designate the same or similarcomponents.

The present disclosure relates to biological or chemical analysis, andmore particularly, to a circuit with sensor(s) connected to a laminatedmanifold for efficient delivery of a liquid reagent to an active surfaceof the sensor(s).

FIG. 1 is a perspective view of one example of a cartridge 100, whichmay be used for, e.g., biological or chemical analysis. In one example,the cartridge may be used to enable sequencing, for example, DNAsequencing, e.g., sequencing-by-synthesis or next-generation sequencing(also known as high-throughput sequencing). In another example, thecartridge may be used to enable genotyping. As one skilled in the artwill know, genotyping involves determining differences in the geneticmake-up (genotype) of an individual by examining the individual's DNAsequence using biological assays and comparing it to anotherindividual's sequence or a reference sequence. The cartridge, which maybe consumable or reusable, includes a reagent rotor 102, a cartridgebody 104 (with pump 107 internal to cartridge body), a laminatedmanifold 106 for delivering the reagent and a circuit 108 with passiveelectronics 109 for various functions of the cartridge and electricalinterconnect 110 for external electrical connection. The laminatedmanifold is used to deliver a liquid reagent to an active surface of asensor (134, FIG. 2), in accordance with one or more aspects of thepresent disclosure. Although the pump in this example is internal to thecartridge, it will be understood that the pump may instead be on asurface of the cartridge or external to the cartridge.

The fluid flow of the reagent from storage (rotor 102 in this example)is active via pump 107. The pump draws the liquid reagent from therotor, through the laminated manifold 106 and to flow cell 119 over theactive surface (138, FIG. 3) of the sensor (134, FIG. 2) through fluidicopening 103. The liquid reagent exits the flow cell to the arms of whatlooks like a candelabra (channels 117). The liquid reagent returns tothe pump through the array of pinch valves 111 located, for example, atthe bottom of the cartridge. The pinch valves may normally be closed,such that which pinch valve is open when the pump aspirates determineswhich arm of the candelabra is used for the return. Any excess fluidfrom channels 117 return to the pump through fluidic path 115 andfluidic opening 105. The microfluidic pump maintains a flow ofreagent(s) through the cartridge for sensing. In one example, the pumptakes the form of a self-priming micro-pump.

Non-limiting examples of the function(s) of the sensor include, forexample, light sensing (e.g., having a predetermined range ofwavelengths sensed), detecting the presence of one or more substances(e.g., biological or chemical substance) and detecting a change inconcentration of something (e.g., ion concentration). The sensor may be,for example, semiconductor-based (e.g., an integrated circuit), theindividual devices of which may be planar or non-planar (e.g., Fin FieldEffect Transistor (FinFET) based). In one example, the sensor may be aCMOS (Complementary Metal-Oxide Semiconductor) image sensor. As oneskilled in the art will know, the circuitry of a CMOS image sensorincludes passive electronic elements, such as a clock and timinggeneration circuit, an analog-to-digital converter, etc., as well as anarray of photodetectors to convert photons (light) to electrons, whichis then converted to a voltage. In another example, the sensor may be aCCD (Charge Coupled Device), another type of image sensor.

As one skilled in the art will understand, “CMOS” refers to a technologyused to fabricate integrated circuits. As used herein, “CMOS sensor” and“CMOS image sensor” refer to sensors fabricated using CMOS technology.The “complementary” aspect of the name refers to the inclusion of bothn-type and p-type metal-oxide semiconductor field effect transistors(MOSFETs) in integrated circuits (ICs) fabricated using CMOS technology.Each MOSFET has a metal gate with a gate dielectric, such as an oxide(hence, the “Metal-Oxide” part of the name) and a semiconductor materialbelow the gate (corresponds to “Semiconductor” in the name). ICs arefabricated on a die, which is a portion of a semiconductor substrate orwafer that is cut out after fabrication, and ICs fabricated using CMOStechnology are characterized by, for example, high noise immunity andlow static power consumption (one of the transistors is always off).

In one example, a CMOS image sensor may include, for example, millionsof photodetectors, also called pixels. Each pixel includes aphotosensor, which accumulates charge from the light, an amplifier toconvert the accumulated charge into a voltage, and a pixel-selectswitch. Each pixel may also include, for example, an individualmicrolens to capture more of the light, or have other enhancements toimprove the image such as, for example, noise reduction.

One example of the fabrication of a semiconductor device fabricatedusing CMOS technology will now be provided. Starting, for example, witha p-type semiconductor substrate, the NMOS region may be protected whilean n-type well is created in the PMOS region. This may be accomplishedusing, for example, one or more lithographic processes. A thin gateoxide and gate (e.g., polysilicon) may then be formed in both the NMOSand PMOS regions. N+ type dopant regions may be formed in the p-typesubstrate of the NMOS region on either side of the dummy gate (i.e., thesource and drain are formed), and one region of the n+ type dopant asthe body (here, the well) contact in the PMOS region. This may beaccomplished using, for example, a mask. The same process of masking anddoping may then be used to form the source and drain in the PMOS regionand the body contact in the NMOS region. Metallization to form theterminals to the various regions of the NMOS and PMOS transistors (i.e.,body, source, drain and gate) may then be performed. Unlike CCDs, CMOSimage sensors may include other circuits on the same chip at little tono extra cost, providing functions such as image stabilization and imagecompression on-chip.

FIG. 2 is an exploded view of one example of the laminated manifold 106of FIG. 1. The laminate includes a lidding layer 112, which may be, forexample, a polymer film (e.g., polyethylene terephthalate (PET) orpoly(methyl methacrylate (PMMA)), and may have a thickness of, e.g.,about 100 microns to about 700 microns in one example, and about 100microns to about 400 microns in another example. The laminated manifoldalso includes a fluidic distribution layer 116 for distributing theliquid reagent(s), which may have a thickness of, for example, about 200microns to about 1000 microns in one example, and about 300 microns toabout 700 microns in another example. Fluidic distribution layer 116 maybe, for example, a material with low or no autofluorescence, e.g., athin plastic film or glass. Non-limiting examples of materials for layer116 include: PMMA, commercially available from, for example, EvonitCorporation, Parsippany, N.J.; a Cobalt Phosphide (CoP) film,commercially available from, for example, American Elements, LosAngeles, Calif.; a Cyclic Olefin Copolymer (COC), commercially availablefrom, for example, Zeon Chemicals L.P., Louisville, Ky.; andborosilicate glass, commercially available from, for example, SchottNorth America, Inc., Elmsford, N.Y. A fluidic path through channels 117for bulk or relatively thick fluid is defined by layer 116. The channelsare sized to enable fluid flow with low impedance, for example, having awidth of between about 0.25 mm and about 1 mm. Between the lidding andfluidic distribution layers is an adhesive layer 114, which may have athickness of, for example, about 20 microns to about 50 microns in oneexample, and about 25 microns in another example. In one example, theadhesive layer may include a pressure-sensitive adhesive for securelyattaching under pressure the layers directly above and below thepressure-sensitive adhesive. Non-limiting examples of the adhesive oflayer 114 include an acrylic or silicone adhesive. Thepressure-sensitive adhesive may be part of, for example, a single-sidedadhesive tape that may include, for example, a rigid plastic liner(e.g., PET) with the adhesive thereon. Such adhesive tapes arecommercially available from, for example, 3M in St. Paul, Minn., orAdhesives Research, Inc. in Glen Rock, Pa. As one skilled in the artwill know, a pressure-sensitive adhesive, when under pressure, creates abond without the need for solvent, water or heat.

The laminated manifold of FIG. 2 further includes a substrate layer 120,and the substrate layer may include an aperture 121, along with layers118 and 122, which overlap openings 123 and 125 in layer 116, allowingreagent(s) to reach the active surface (138, FIG. 3) of the sensor fromthe channels in layer 116. In one example, the openings are sizedsimilar to the channels. The substrate layer may have a thickness of,for example, about 50 microns to about 70 microns in one example, andabout 60 microns in another example. Substrate layer 120 may be, forexample, a polymer film (e.g., PET or PMMA). The fluid flow over thesensor transitions from the relatively thick flow in the channels of thefluidic distribution layer to a relatively thin fluid flow, whichprovides an efficient use of the fluid. The fluidic path over the sensoris shown through flow line 156 in FIG. 4. In one example, a chemicalreaction of only the fluid passing over the sensor, for example,fluorescence, may be observable to a user. Between the fluidicdistribution layer and the substrate layer is an adhesive layer 118,which may have a thickness of, for example, about 20 microns to about 50microns in one example, and about 25 microns in another example. In oneexample, layer 118 may include a pressure-sensitive adhesive forsecurely attaching under pressure the layers directly above and belowthe pressure-sensitive adhesive. Non-limiting examples of the adhesiveof layer 118 include an acrylic or silicone adhesive. Thepressure-sensitive adhesive may be part of, for example, a double-sidedadhesive tape that may include, for example, a rigid plastic liner(e.g., PET) with the adhesive thereon. Such adhesive tapes arecommercially available as described above. The structure furtherincludes a planarization layer 124 to provide support to the laminatedmanifold and to present an even surface to the circuit 108, which mayhave a thickness of, for example, about 500 microns to about 700 micronsin one example, and about 600 microns in another example, in accordancewith one or more aspects of the present disclosure. In one example, theplanarization layer is about the same thickness as the die. In oneexample, the material of the planarization layer 124 may includeextruded plastic, for example, PET, polypropylene or polycarbonate.Between substrate layer 120 and planarization layer 124 is an adhesivelayer 122, which may have a thickness of, for example, about 20 micronsto about 50 microns in one example, and about 25 microns in anotherexample. In one example, layer 122 may include a pressure-sensitiveadhesive for securely attaching under pressure the layers directly aboveand below the pressure-sensitive adhesive. Non-limiting examples of theadhesive of layer 122 include an acrylic or silicone adhesive. Thepressure-sensitive adhesive may be part of, for example, a double-sidedadhesive tape that may include, for example, a rigid plastic liner(e.g., PET) with the adhesive thereon. Such adhesive tapes arecommercially available as described above.

The laminated manifold 106 may be bonded to circuit 108, for example,via bonding layer 126, which may include, for example, apressure-sensitive adhesive with a thickness of, e.g., about 50 micronsto about 70 microns in one example, and about 60 microns in anotherexample. Non-limiting examples of the adhesive of layer 126 include anacrylic or silicone adhesive. The pressure-sensitive adhesive may bepart of, for example, a single-sided adhesive tape that may include, forexample, a rigid plastic liner (e.g., PET) with the adhesive thereon.Such adhesive tapes are commercially available as described above. Thecircuit may be flexible or rigid (e.g., PCB board) and have a thicknessof, for example, about 200 microns to about 300 microns in one example,and about 250 microns in another example.

Both the planarization layer 124 and bonding layer 126 include a cut-out132 for a sensor 134 on the circuit such that the active surface (138,FIG. 3) may be substantially planar with the laminated manifold when thereagent is in contact with the active surface. Finally, the circuit isbonded to the cartridge body 104 via bonding layer 130, which mayinclude a pressure-sensitive adhesive and may have a thickness of, forexample, about 50 microns to about 150 microns in one example, and about100 microns in another example. Non-limiting examples of the adhesive oflayer 130 include an acrylic or silicone adhesive. Thepressure-sensitive adhesive may be part of, for example, a double-sidedadhesive tape that may include, for example, a rigid plastic liner(e.g., PET) with the adhesive thereon. Such adhesive tapes arecommercially available as described above.

FIG. 3 is a perspective view of one example of sensor 134 in relation tothe laminated manifold 106 and circuit 108. The active surface of thesensor and the laminated manifold structure surrounding and above thesensor (i.e., fluidic distribution layer 116, FIG. 2) where thereagent(s) are introduced, constitutes a flow cell. A flow cell channel136 delivers liquid reagent(s) to an active surface 138 of thesensor(s), situated on die 140, and then carries the liquid reagent(s)away from the sensor. Substance(s), for example, biological or chemicalsubstances(s), may be introduced into the space for on-chip sensing bythe active surface of the sensor. Where semiconductor based, the sensormay be fabricated on a silicon substrate (e.g., a silicon wafer), whichbecomes the die when cut from the silicon wafer. The thickness of thedie depends on the size (diameter) of the silicon wafer. For example, astandard silicon wafer with a 51 mm diameter may have a thickness ofabout 275 microns, while a standard silicon wafer with a diameter of 300mm may have a thickness of about 775 microns. As used herein, the activearea of the sensor(s) refers to the sensor surface that will come intocontact with the reagent(s) for sensing. There may be more than onesensor on the die, and different sensors may be included on the samedie. The flow cell channel may include, for example, silicate glass(e.g., aluminosilicate glass). The die is sealed at sealing areas 142.In one example, each sealing area includes, for example, a bridgeadhesive 144, structural adhesive 146 and wire bonding 148 using, forexample, gold wire, which is covered by a wire bond encapsulate 150, inaccordance with one or more aspects of the present disclosure. The diemay be attached to circuit 108 by an adhesive, for example, a dispersedultraviolet-curable adhesive or a pressure-sensitive adhesive tape(e.g., acrylic or silicon adhesive). Electrical connection between thecircuit and the sensor may be accomplished a number of ways, forexample, low-temperature wire bonding, which prevents exposure of thedie to high temperatures. The wire bonds are relatively small and may beultrasonically welded wires that make electrical connections between thesensor and the circuit. These electrical connections may be protectedwith, for example, an adhesive dispersed on the wires (e.g., anultraviolet (UV)-curable adhesive), which completely encapsulates thewires when cured with UV light, transforming into a solid form. Acommercially available UV-curable adhesive may be obtained from, forexample, Dymax Corporation, Torrington, Conn. The interface 141 betweenthe die 140 and the manifold's fluidic channel is sealed so that theactive surface of the sensor comes into contact with the fluid(s) in thelaminated manifold, while also isolating the liquid from electricalinterconnects and other aspects of the circuit that may be shorted outby the presence of electrically conductive liquid.

FIG. 4 is a perspective view of one example of a cross-section of thesensor area taken across line 152 of FIG. 3. As shown, an inlet 103 froma reagent reservoir (e.g., within reagent rotor 102 shown in FIG. 1)distributes the reagent via force of the pump (107, FIG. 1) to a flowline 156 connected to flow cell channel 136 over active surface 138 ofthe sensor, in accordance with one or more aspects of the presentdisclosure.

FIGS. 5-10 depict various stages of constructing the cartridge 100 ofFIG. 1. FIG. 5 is a perspective view of one example of circuit 108 withsensor 134 attached thereto, for example, bonded together, in accordancewith one or more aspects of the present disclosure.

FIG. 6 depicts attaching planarization layer 124 to the circuit 108 ofFIG. 5 by, for example, using a bonding layer 126, in accordance withone or more aspects of the present disclosure.

FIG. 7 depicts dispensing and curing bridge adhesive 144 to thestructure of FIG. 6, in accordance with one or more aspects of thepresent disclosure.

FIG. 8 depicts one example of attaching a laminated manifold 106 (e.g.,as described with respect to FIG. 2) to the planarization layer 124 oncircuit 108 of FIG. 7 via, for example, using bonding layer 122 (FIG.2), in accordance with one or more aspects of the present disclosure.

FIG. 9 depicts one example of wire bonding 148 the structure of FIG. 8,for example, low-temperature wire bonding, encapsulating the wirebonding via, for example, wire bond encapsulant 150 and attaching flowcell channel 136, a V-shaped extension of the fluidic pathway onopposite sides of the sensor delivering the reagent(s) to the activesurface of the sensor for sensing, in accordance with one or moreaspects of the present disclosure. The wire bond may include a metal,for example, aluminum, copper, silver or gold.

FIG. 10 depicts one example of attaching the structure of FIG. 9 to thereagent rotor 102 and cartridge body 104, for example, by bonding usingbonding layer 130 (FIG. 2), which may include an adhesive (e.g., apressure-sensitive adhesive as previously described), in accordance withone or more aspects of the present disclosure.

In a first aspect, disclosed above is an apparatus. The apparatusincludes a circuit and sensor(s) on a die attached to the circuit, thecircuit including an electrical interconnect for external electricalconnection, and a laminated manifold attached to the circuit to delivera liquid reagent over an active surface of the sensor(s), the laminatedmanifold including fluidic channel(s), an interface between the die andthe fluidic channel(s) being sealed.

In one example, the sensor(s) may include, for example, a semiconductor.In another example, the sensor(s) may take the form of, for example, aComplementary Metal-Oxide Semiconductor (CMOS) sensor (e.g., a CMOSimage sensor).

In one example, the laminated manifold in the apparatus of the firstaspect may include, for example, multiple layers that may include, forexample, a top lidding layer, a fluidic distribution layer, a substratelayer, and a bottom planarization layer. In one example, the circuit maybe, for example, bonded to the planarization layer, and theplanarization layer may have, for example, a thickness that is about acollective thickness of the sensor(s) and die.

In one example, a pressure-sensitive adhesive may be, for example,between adjacent layers of the multiple layers of the laminatedmanifold.

In one example, adjacent layers of the laminated manifold may be, forexample, mechanically connected, for example, via fasteners or screws.

In one example, the apparatus of the first aspect may be, for example,part of a cartridge, such as that used for biological analysis.

In one example, the apparatus of the first aspect may be, for example,part of a cartridge, such as that used for chemical analysis.

In one example, the apparatus of the first aspect may be, for example,part of a cartridge, and the cartridge may further include, for example,a reagent storage and delivery system coupled to the laminated manifold,and a cartridge body and a reagent pump coupled to the reagent storageand delivery system.

In one example, the laminated manifold in the apparatus of the firstaspect may have, for example, cut-out(s) for the die. In one example,the die may be, for example, wire bonded to the circuit.

In one example, the apparatus of the first aspect, when in use, areagent may be, for example, delivered via the laminated manifold overan active surface of the sensor(s). In one example, only the activesurface(s) of the sensor(s) is (are) exposed to the reagent.

In a second aspect, disclosed above is a method. The method includesassembling a laminated manifold, the laminated manifold includingfluidic channel(s), attaching a die with sensor(s) to a circuit, thecircuit including an electrical interconnect. The method furtherincludes attaching a planarization layer to the circuit, theplanarization layer including a cut out for the die, placing sealingadhesive at sides of the die, attaching the laminated manifold to thecircuit, and sealing an interface between the die and the fluidicchannel(s), the laminated manifold and attached circuit together beingan assembly.

In one example, the method may further include, for example, attachingthe assembly to a cartridge.

In one example, assembling the laminated manifold in the method of thesecond aspect may include, for example, laminating layers, and thelayers may include, for example, a top lidding layer, a fluidicdistribution layer, a substrate layer, and a bottom planarization layer.In one example, the laminating may include, for example, using anadhesive between adjacent layers (e.g., a pressure-sensitive adhesive).

In one example, the method of the second aspect may further include, forexample, using the assembly for sequencing.

In one example, the method of the second aspect may further include, forexample, using the assembly for genotyping.

While several aspects of the present disclosure have been described anddepicted herein, alternative aspects may be effected by those skilled inthe art to accomplish the same objectives. Accordingly, it is intendedby the appended claims to cover all such alternative aspects.

It should be appreciated that all combinations of the foregoing concepts(provided such concepts are not mutually inconsistent) are contemplatedas being part of the inventive subject matter disclosed herein. Inparticular, all combinations of claimed subject matter appearing at theend of this disclosure are contemplated as being part of the inventivesubject matter disclosed herein.

1. Apparatus, comprising: a circuit and at least one sensor on a dieattached to the circuit, the circuit comprising an electricalinterconnect for external electrical connection; and a laminatedmanifold attached to the circuit to deliver a liquid reagent over anactive surface of the at least one sensor, the laminated manifoldcomprising at least one fluidic channel, wherein an interface betweenthe die and the at least one fluidic channel is sealed.
 2. The apparatusof claim 1, wherein the at least one sensor comprises a semiconductor.3. The apparatus of claim 2, wherein the at least one sensor comprises aComplementary Metal-Oxide Semiconductor (CMOS) sensor.
 4. The apparatusof claim 1, wherein the laminated manifold comprises a plurality oflayers, the plurality of layers comprising: a top lidding layer; afluidic distribution layer; a substrate layer; and a bottomplanarization layer.
 5. The apparatus of claim 4, wherein the circuit isbonded to the planarization layer, and wherein the planarization layerhas a thickness that is about a collective thickness of the at least onesensor and die.
 6. The apparatus of claim 4, wherein between adjacentlayers of the plurality of layers is a pressure-sensitive adhesive. 7.The apparatus of claim 4, wherein adjacent layers of the plurality oflayers are mechanically connected.
 8. The apparatus of claim 1, whereinthe apparatus is part of a cartridge for biological analysis.
 9. Theapparatus of claim 1, wherein the apparatus is part of a cartridge forchemical analysis.
 10. The apparatus of claim 1, wherein the apparatusis part of a cartridge, and wherein the cartridge further comprises: areagent storage and delivery system coupled to the laminated manifold;and a cartridge body and a reagent pump coupled to the reagent storageand delivery system.
 11. The apparatus of claim 1, wherein the laminatedmanifold has at least one cut-out for the die.
 12. The apparatus ofclaim 11, wherein the die is wire bonded to the circuit.
 13. Theapparatus of claim 1, wherein when in use, a reagent is delivered viathe laminated manifold over an active surface of the at least onesensor.
 14. The apparatus of claim 13, wherein only the active surfaceof the at least one sensor is exposed to the reagent.
 15. A method,comprising: assembling a laminated manifold, the laminated manifoldcomprising at least one fluidic channel; attaching at least one sensoron a die to a circuit, the circuit comprising an electricalinterconnect; attaching a planarization layer to the circuit, theplanarization layer comprising a cut out for the die; placing sealingadhesive at sides of the die; attaching the laminated manifold to thecircuit; and sealing an interface between the die and the at least onefluidic channel; wherein the laminated manifold and attached circuittogether comprise an assembly.
 16. The method of claim 15, furthercomprising attaching the assembly to a cartridge.
 17. The method ofclaim 15, wherein assembling the laminated manifold comprises laminatinga plurality of layers, the plurality of layers comprising: a top liddinglayer; a fluidic distribution layer; a substrate layer; and a bottomplanarization layer.
 18. The method of claim 17, wherein the laminatingcomprises using a pressure-sensitive adhesive between adjacent layers ofthe plurality of layers.
 19. The method of claim 15, further comprisingusing the assembly for sequencing.
 20. The method of claim 15, furthercomprising using the assembly for genotyp